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e.g., in 2014, 8.5% of adults aged 18 or more had diabetes but in 2019, and 1.5 million of death took place by direct diabetes

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Notably, breast cancer cells achieve metabolic adaptation by hijacking the autophagy mechanism: under glucose-deprivation conditions, MANF-mediated mitophagy eliminates dysfunctional mitochondria through the PRKN/Parkin-dependent pathway, maintains the ATP supply and promotes tumour survival [112], suggesting that targeting the MANF‒PRKN interaction can break the drug resistance barrier of breast cancer under metabolic stress